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Iron Dysregulation in Mitochondrial Dysfunction and Alzheimer's Disease.
Onukwufor, JO, Dirksen, RT, Wojtovich, AP
Antioxidants (Basel, Switzerland). 2022;11(4)
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Alzheimer’s disease (AD) is a progressive deterioration of the brain and memory, for which there is currently no cure. Important to the normal function of the brain is a tightly regulated iron supply and dysregulation in this process may be involved in the development of AD. This review paper aimed to determine how iron dysfunction is related to energy production in the brain and how a type of programmed cell death, that is controlled by iron, may be involved in the development of AD and targeted as a potential treatment. The paper reviewed how iron is regulated, with deficiency sensed by iron regulatory proteins (IRPs), which ultimately results in the release and transport of iron around the body and increased uptake in the diet. If these IRPs become impaired, then a dysregulation of iron levels can occur. Increases in brain iron levels have been associated with progressive development of AD and some areas of the brain are more susceptible than others especially the hippocampus, which is responsible for learning and memory. Increased iron levels in the brain maybe age dependent and associated with cognitive decline in individuals with AD. The mechanisms behind this were discussed and dysregulated iron alongside dysfunctional energy production has been observed in individuals with AD. There is some uncertainty on the causes of this, however it may involve the accumulation of iron which damages lipid membranes around the brain cells, causing them to die in a reaction known as ferroptosis. It was concluded that iron may have a pivotal role in the development of AD due to its importance for energy production and the prevention of brain cell death. This study could be used by healthcare professionals to understand that low iron levels may be involved in the development of AD and that checking and correcting any deficiencies may be of benefit.
Abstract
Alzheimer's disease (AD) is a devastating progressive neurodegenerative disease characterized by neuronal dysfunction, and decreased memory and cognitive function. Iron is critical for neuronal activity, neurotransmitter biosynthesis, and energy homeostasis. Iron accumulation occurs in AD and results in neuronal dysfunction through activation of multifactorial mechanisms. Mitochondria generate energy and iron is a key co-factor required for: (1) ATP production by the electron transport chain, (2) heme protein biosynthesis and (3) iron-sulfur cluster formation. Disruptions in iron homeostasis result in mitochondrial dysfunction and energetic failure. Ferroptosis, a non-apoptotic iron-dependent form of cell death mediated by uncontrolled accumulation of reactive oxygen species and lipid peroxidation, is associated with AD and other neurodegenerative diseases. AD pathogenesis is complex with multiple diverse interacting players including Aβ-plaque formation, phosphorylated tau, and redox stress. Unfortunately, clinical trials in AD based on targeting these canonical hallmarks have been largely unsuccessful. Here, we review evidence linking iron dysregulation to AD and the potential for targeting ferroptosis as a therapeutic intervention for AD.
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The Malnutritional Status of the Host as a Virulence Factor for New Coronavirus SARS-CoV-2.
Briguglio, M, Pregliasco, FE, Lombardi, G, Perazzo, P, Banfi, G
Frontiers in medicine. 2020;7:146
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This opinion article explores the role of an individual’s nutrition status when subjected to infection by viruses, in particular Covid-19. Distinction is made between the susceptibility to infection in the first instance and the ability to persist in fighting infection once it is established. For Covid-19, it is argued that a healthier nutritional status, in particular Vitamins A, B, C, D and E, iron selenium and zinc, will lower susceptibility to infection, lower the severity of the virus and therefore reduce the length of time an individual has to find reserves to fight the virus. More severe cases of Covid-19 infection also often include gastro-intestinal symptoms which further exacerbate nutritional status with lowered appetite. The authors conclude that malnourished individuals may be more susceptible to Covid-19 infection and that nutritional support is vital in severe cases. The article includes a useful diagram of both hyponutrition and hypernutrition and possible impacts of Covid-19.
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action.
Naja, F, Hamadeh, R
European journal of clinical nutrition. 2020;74(8):1117-1121
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This Lebanese articled provides a commentary on the evolving COVID-19 pandemic and aims to give a framework for Nutritional action to help the physical and mental health of individuals, communities, and nations. At an individual level the focus is on the link between diet and immunity and the profound effect diet has on people’s immune system and disease susceptibility. An adequate intake of iron, zinc, and vitamins A, E, B6, and B12 is predominantly vital for the maintenance of immune function. Individuals should aim to eat as healthily as possible, including a wide range of fruits and vegetables, limit snacking, take regular exercise and get an adequate amount of sleep to support their health. Single foods promising cures or prevention of infection are unfounded claims which can give a false sense of security. The focus for communities is on food availability, for nations its food security and on a global level it is about food trade agreements. Its important to protect against hoarding and panic buying to ensure enough food for everyone. National economic instability during COVID-19 can lead to a risk of food security so governments are advised to support local agricultural produce and reduce their reliance on imported goods. Global supply chains and agreements need to be respected to lessen the impact further down the supply chain. The health of each individual has a direct impact on the community and nation and is a direct consequence of their dietary awareness and choices.
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Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.
Gasmi, A, Noor, S, Tippairote, T, Dadar, M, Menzel, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;215:108409
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With the continuing spread of COVID-19 and lack of any approved treatments, this paper examines possible strategies for prevention. The data emerging so far highlights that individual health status plays a critical role in determining clinical severity of COVID-19 symptoms ranging from asymptomatic, mild, moderate, to death. Metabolic status, as determined by a patient’s diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors can therefore be considered preventative strategies to improve the severity of COVID-19 outcomes. Social distancing and personal hygiene are stated as the most effective strategies to prevent or slow spread of the disease. However individual health status, age and the presence of pre-existing comorbidities influences outcomes, as shown by global data highlighting a prevalence in older, males with metabolic conditions; hypertension in 23.7% patients and diabetes in 16.2% of patients. Older males appear more prone to infectious diseases with high pro-inflammatory immune responses and low adaptive immune responses than an older woman. Diet and healthy intestinal and respiratory tract microbiota may also influence immune system competence. Numerous micronutrients are essential for immunocompetence, particularly vitamin A, C, D, E, Bs, iron, selenium, and zinc. A balanced diet, high in colourful fruits and vegetables with a variation of prebiotic fibres, probiotics, and plant polyphenols and phytonutrients, help promote a healthy, diverse microbiota. Oral probiotics may also be beneficial to vulnerable individuals. Vitamin D supplementation is also proving helpful in prevention of acute respiratory tract infections. Other lifestyle factors such as smoking and exposure to environmental toxins should also be considered. Together these preventative measures may reduce personal risk of getting the disease.
Abstract
It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.
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Nutritional Interventions in the Management of Fibromyalgia Syndrome.
Pagliai, G, Giangrandi, I, Dinu, M, Sofi, F, Colombini, B
Nutrients. 2020;12(9)
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Fibromyalgia (FM) is a chronic pain condition, often presenting with widespread body pain, joint stiffness, sleep disorders, depression, anxiety, gastrointestinal and cognitive complaints. Despite being common, the cause of FM is not well understood. In the absence of effective treatments, the current management of FM involves a multidisciplinary approach utilizing pharmacological and non-pharmacological interventions. Growing evidence suggests a role for nutrition as a complementary strategy for FM management. This brief review summarises the possible impact of nutritional supplements and dietary interventions on FM. Previous reviews concluded that vitamin and mineral deficiencies themselves are unlikely to be significant in the development of FM. Yet, a few interventional studies investigating the use of Vitamin D, magnesium, iron and probiotics showed promising results. To date, there is no or limited evidence for the use of Vitamin C, E, selected amino acids, botanical or antioxidant supplements. Food-wise the inclusion of quality olive oil and the grain Khorasan proved helpful on FM presentation, whilst findings around the role of dietary monosodium glutamate and aspartame seem mixed. Regarding diet patterns, gluten-free, low-calorie, vegetarian, vegan, raw food or Mediterranean diets were all associated with improvement of symptoms. Equally a FODMAP diet can aid FM associated digestive complaints due to the significant overlap of Irritable Bowel Syndrome with FM. The authors concluded that the clinical application of dietary supplements in the management of FM remains controversial. Yet, dietary interventions appear to be an effective tool in the management of FM. Since various diet interventions demonstrated benefits, dietary adequacy and weight loss may be most critical from a clinical perspective.
Abstract
Fibromyalgia (FM) is a multifactorial syndrome of unknown etiology, characterized by widespread chronic pain and various somatic and psychological manifestations. The management of FM requires a multidisciplinary approach combining both pharmacological and nonpharmacological strategies. Among nonpharmacological strategies, growing evidence suggests a potential beneficial role for nutrition. This review summarizes the possible relationship between FM and nutrition, exploring the available evidence on the effect of dietary supplements and dietary interventions in these patients. Analysis of the literature has shown that the role of dietary supplements remains controversial, although clinical trials with vitamin D, magnesium, iron and probiotics' supplementation show promising results. With regard to dietary interventions, the administration of olive oil, the replacement diet with ancient grains, low-calorie diets, the low FODMAPs diet, the gluten-free diet, the monosodium glutamate and aspartame-free diet, vegetarian diets as well as the Mediterranean diet all appear to be effective in reducing the FM symptoms. These results may suggest that weight loss, together with the psychosomatic component of the disease, should be taken into account. Therefore, although dietary aspects appear to be a promising complementary approach to the treatment of FM, further research is needed to provide the most effective strategies for the management of FM.
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The Role of Iron in Brain Development: A Systematic Review.
McCann, S, Perapoch Amadó, M, Moore, SE
Nutrients. 2020;12(7)
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Iron deficiency is the most common vitamin or mineral deficiency worldwide and is particularly common among pregnant women, infants and young children due to high iron demands during periods of rapid growth. Iron plays an important role in the development of the brain, and animal studies suggest that getting enough iron in pregnancy and early childhood is particularly important. The aims of this systematic review were to (i) investigate the relationship between iron status and brain development and (ii) assess whether this relationship differs according to age or type of development (‘domain’). The researchers looked for studies on iron deficiency or iron supplementation in pregnancy and up to 4 years of age. 26 observational studies and 28 intervention studies were included in the review. There was no clear relationship between iron status and developmental outcomes across any of the ages or domains included. Many of the studies were of low quality and there was a wide variation in study design, along with a lack of research on pregnancy and early infancy. The researchers concluded that evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
Abstract
One-third of children falter in cognitive development by pre-school age. Iron plays an important role in many neurodevelopmental processes, and animal studies suggest that iron sufficiency in pregnancy and infancy is particularly important for neurodevelopment. However, it is not clear whether iron deficiency directly impacts developmental outcomes, and, if so, whether impact differs by timing of exposure or developmental domain. We searched four databases for studies on iron deficiency or iron supplementation in pregnancy, or at 0-6 months, 6-24 months, or 2-4 years of age. All studies included neurodevelopmental assessments in infants or children up to 4 years old. We then qualitatively synthesized the literature. There was no clear relationship between iron status and developmental outcomes across any of the time windows or domains included. We identified a large quantity of low-quality studies, significant heterogeneity in study design and a lack of research focused on pregnancy and early infancy. In summary, despite good mechanistic evidence for the role of iron in brain development, evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.
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Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.
Martín-Masot, R, Nestares, MT, Diaz-Castro, J, López-Aliaga, I, Alférez, MJM, Moreno-Fernandez, J, Maldonado, J
Nutrients. 2019;11(11)
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Anaemia is a common clinical expression of Celiac Disease (CD) alongside vitamin B12, iron and folate deficiencies. This review looks at the latest evidence and effects of a gluten free diet, the mainstay of treatment for CD. Typically, symptoms subside whilst adhering to a GF diet however in 20% of people anaemia and nutrient deficiencies can persist. Some of this is attributed to lack of adherence to the diet, oftentimes accidental given the wide range of foods containing gluten. This in turn leads to further damage of the intestine and can be difficult to detect and monitor effectively. Inflammation of the gastrointestinal tract, and malabsorption, are the main reasons for nutrient deficiencies leading to anaemia in CD. Iron is a critical nutrient which can easily be affected by damage to the intestinal villi, common in CD, and over time lead to iron deficiency anaemia as the body is unable to absorb dietary iron and the body’s iron stores are depleted. Likewise, absorption of vitamins B12 and B9 (folate) are also impaired by damaged villi and vitamin B12 is further affected by small intestine injuries including decreased gastric acid production, bacterial overgrowth and reduced intrinsic factor efficiency. Deficiencies of these two nutrients can lead to macrocytic anaemia with low blood cell volumes. Overall a gluten free diet is shown to reduce symptoms of CD in a matter of weeks. The more patients adhere to the diet, the more the risk of nutrient deficiencies and anaemia reduces.
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
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The Role of Mineral and Trace Element Supplementation in Exercise and Athletic Performance: A Systematic Review.
Heffernan, SM, Horner, K, De Vito, G, Conway, GE
Nutrients. 2019;11(3)
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Minerals and trace elements (MTEs) are involved in hundreds of biological processes, and according to available population data many recommended amounts of MTEs are not being met. While MTEs are known to impact processes that are related to athletic performance, there is no consensus as to the efficacy of MTE supplementation and improved performance. The aim of this systematic review was to critically analyse the available evidence on MTE supplementation for enhancing athletic performance. According to 128 studies that met the inclusion criteria, iron and magnesium were the only two that demonstrated benefits. Based on the existing literature, the authors conclude there is insufficient evidence to suggest guidelines of MTEs to enhance athletic performance, and encourage high quality studies to investigate this further.
Abstract
Minerals and trace elements (MTEs) are micronutrients involved in hundreds of biological processes. Deficiency in MTEs can negatively affect athletic performance. Approximately 50% of athletes have reported consuming some form of micronutrient supplement; however, there is limited data confirming their efficacy for improving performance. The aim of this study was to systematically review the role of MTEs in exercise and athletic performance. Six electronic databases and grey literature sources (MEDLINE; EMBASE; CINAHL and SportDISCUS; Web of Science and clinicaltrials.gov) were searched, in accordance with PRISMA guidelines. Results: 17,433 articles were identified and 130 experiments from 128 studies were included. Retrieved articles included Iron (n = 29), Calcium (n = 11), Magnesium, (n = 22), Phosphate (n = 17), Zinc (n = 9), Sodium (n = 15), Boron (n = 4), Selenium (n = 5), Chromium (n = 12) and multi-mineral articles (n = 5). No relevant articles were identified for Copper, Manganese, Iodine, Nickel, Fluoride or Cobalt. Only Iron and Magnesium included articles of sufficient quality to be assigned as 'strong'. Currently, there is little evidence to support the use of MTE supplementation to improve physiological markers of athletic performance, with the possible exception of Iron (in particular, biological situations) and Magnesium as these currently have the strongest quality evidence. Regardless, some MTEs may possess the potential to improve athletic performance, but more high quality research is required before support for these MTEs can be given. PROSPERO preregistered (CRD42018090502).
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Low Zinc, Copper, and Manganese Intake is Associated with Depression and Anxiety Symptoms in the Japanese Working Population: Findings from the Eating Habit and Well-Being Study.
Nakamura, M, Miura, A, Nagahata, T, Shibata, Y, Okada, E, Ojima, T
Nutrients. 2019;11(4)
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Diet, as well as other lifestyle factors (sleep, exercise etc) are thought to play a significant role in the occurrence of mental disorders, including depression and anxiety. This study focused on the dietary intake of particular minerals (zinc, copper and manganese) and their effects on depression and anxiety of 2089 Japanese participants, each in full time employment. Reasons for the occurrence of mental disorders are considered multi-factorial, but insufficient mineral intake (particularly zinc) is believed to be a causal factor in the prevalence of depression and anxiety. Results of this cross-sectional study showed that low intake of zinc, copper and manganese was associated with depression and anxiety symptoms. More specifically, the effect of both low zinc and low copper intake indicated a higher susceptibility towards depression with both low and high manganese status, suggesting low zinc and copper intake contributes to depression and anxiety symptoms regardless of manganese status. Researchers acknowledge that more investigation is needed.
Abstract
Epidemiological studies have suggested that there is an association between diet and mental health. The aim of this study was to investigate the association between the intake of six minerals and mental disorders in a cross-sectional study. We used data from the Eating Habit and Well-being study in Japanese workers. Kessler's six-item psychological distress scale was used to detect mental disorders, with a cut-off score of 12/13, and a validated food frequency questionnaire was used to estimate dietary mineral intake. A total of 2089 participants with no history of depression were included. The prevalence of mental disorders was 6.9%. The lowest quartiles of zinc, copper, and manganese intakes were associated with mental disorders, whereas the lowest quartiles of calcium, magnesium, and iron intake were not associated with mental disorders. Combination analysis of high (≥median) or low (
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Micronutrient Status of Recreational Runners with Vegetarian or Non-Vegetarian Dietary Patterns.
Nebl, J, Schuchardt, JP, Ströhle, A, Wasserfurth, P, Haufe, S, Eigendorf, J, Tegtbur, U, Hahn, A
Nutrients. 2019;11(5)
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There is current debate as to whether plant-based nutrition can provide all the required nutrients in adequate amounts for athletes. The aim of this cross-sectional study was to evaluate the micronutrient status among omnivore, vegetarian and vegan recreational runners. In this study, fasting blood levels of vitamin B12, folate, vitamin D, iron, calcium, magnesium and zinc were assessed in 27 omnivores, 26 vegetarians and 28 vegans. These results showed there were no significant differences between vegan and vegetarian diets compared with the omnivore diet. Based on these results, the authors conclude a well-planned vegetarian and vegan diet, including supplementation, can meet the recreational runner’s requirements of important micronutrients. The authors suggest further research be done on a larger sample size and on athletes of differing levels of performance intensity.
Abstract
Vegetarian diets have gained popularity in sports. However, few data exist on the status of micronutrients and related biomarkers for vegetarian and vegan athletes. The aim of this cross-sectional study was to compare the micronutrient status of omnivorous (OMN, n = 27), lacto-ovo-vegetarian (LOV, n = 26), and vegan (VEG, n = 28) recreational runners. Biomarkers of vitamin B12, folate, vitamin D, and iron were assessed. Additionally, serum levels of calcium, magnesium, and zinc were examined. Lifestyle factors and supplement intake were recorded via questionnaires. About 80% of each group showed vitamin B12 adequacy with higher levels in supplement users. Mean red blood cell folate exceeded the reference range (>340 nmol/L) in all three groups (OMN: 2213 ± 444, LOV: 2236 ± 596, and VEG: 2354 ± 639 nmol/L; not significant, n.s.). Furthermore, vitamin D levels were comparable (OMN: 90.6 ± 32.1, LOV: 76.8 ± 33.7, and VEG: 86.2 ± 39.5 nmol/L; n.s.), and we found low prevalence (<20%) of vitamin D inadequacy in all three groups. Less than 30% of each group had depleted iron stores, however, iron deficiency anemia was not found in any subject. Our findings suggest that a well-planned, health-conscious lacto-ovo-vegetarian and vegan diet, including supplements, can meet the athlete's requirements of vitamin B12, vitamin D and iron.